Lysophosphatidic acid potentiates the thrombin-induced production of arachidonate metabolites in platelets.
Concentrations (1 to 20 microM) of 1-oleoyl-lysophosphatidic acid which alone do not affect platelet metabolism of arachidonic acid, do augment the effects of suboptimal concentrations of thrombin on the formation of [14C]phosphatidic acid and the production of [14C]arachidonate metabolites from platelets prelabeled with [14C]arachidonate. The effect on [14C]phosphatidate occurs with concentrations of thrombin (0.1 unit/ml) which are lower than those (0.2 unit/ml) needed to observe the effects on [14C]arachidonate metabolites. The effect of 1-oleoyl-lysophosphatidic acid (10 microM) plus thrombin (0.2 unit/ml) on the formation of phosphatidic acid temporally precedes the production of arachidonate metabolites consistent with a sequential activation of phosphatidylinositol-specific phospholipase C and phospholipase A2 activities. Preincubation of platelets with (32P)orthophosphate shows that the phosphatidic acid formed by 1-oleoyl-lysophosphatidic acid (10 microM) plus thrombin (0.2 unit/ml) is derived from phosphatidylinositol. The Ca2+-ionophoretic properties of lysophosphatidic acid might explain the accumulation of phosphatidic acid since Ca2+ prevents the conversion of phosphatidic acid to phosphatidylinositol. That effect of lysophosphatidic acid is inhibited by prostacyclin, possibly through a cyclic-AMP-mediated effect on calcium homeostasis.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D004357:Drug Synergism; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008246:Lysophospholipids; D010712:Phosphatidic Acids / Q000097:blood* / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology*
D001095:Arachidonic Acids; D008246:Lysophospholipids; D010712:Phosphatidic Acids; D016718:Arachidonic Acid; D011464:Epoprostenol; D013917:Thrombin; C032881:lysophosphatidic acid